The subject of this research is a study of increased protease release by the rapidly metastasizing mouse melanoma (F10) as compared to the slow metastasizing mouse melanoma (F1). The mechanisms of the differential rates of release of the proteases will be studied and partial purification and characterization of proteases attempted. The etiologic relationship between proteases and metastatic spread of the tumor will be explored using specific inhibitors as therapeutic agents in mice injected with F10 cells. The cyclic nucleotide system (both cyclic AMP, and cyclic GMP) of F1 and F10 melanoma cells will be characterized both in vitro and in vivo. Differences in the cyclic nucleotide response to various hormones will be used as a possible measure of membrane alterations in these cells. Attempts will be made to reduce the number of metastases produced by F10 cells by manipulating its cyclic nucleotide system.